Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.     

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.     

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.     

Human lung cancer cell lines express cell membrane complement inhibitory proteins and are extremely resistant to complement-mediated lysis; a comparison with normal human respiratory epithelium in vitro,and an insight into mechanism(s) of resistance

Human lung cancer expresses cell membrane complement inhibitory proteins (CIP). We investigated whether human lung cancer cell lines also express cell-membrane CIP molecules and whether the biology of CIP molecules in these cell lines differs from that of CIP in normal human respiratory epithelium in culture. The cell lines ChaGo K-1 and NCI-H596 were compared with normal human nasal epithelium in primary cultures in respect to the level of cell membrane CIP expression of membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55) and CD59, in respect to the level of cell resistance to complement-mediated lysis, and in respect to the contribution of cell membrane CIP to cell resistance against complement-mediated lysis. We found, using flow cytometry, that both human lung cancer cell lines expressed MCP, DAF and CD59, as did normal nasal epithelial cells. However, normal cells showed a large subpopulation of low DAF-expressing cells (60% of all cells) and a smaller subpopulation of high DAF-expressing cells (40%), while the lung cancer cell lines showed only one cell population, of high DAF expression. In addition, both lung cancer cell lines expressed higher MCP levels, and NCI-H596 cells showed higher levels of CD59. Cell resistance to complement-mediated lysis of both lung cancer cell lines was much higher than that of normal cells. Fifty percent normal human serum, under the same concentrations of complement activators, induced lysis of less than a mean of 10% of lung cancer cells, while lysing up to a mean of 50% of nasal epithelial cells. Lung cancer cell resistance to complement was due to its ability to prevent significant activation of complement upon its cell membrane, as manifested by a failure of complement activators to increase cell membrane deposition of C3-related fragments. The exact mechanism for this resistance remains obscure. Unexpectedly, neutralizing antibodies, anti-MCP and anti-DAF were entirely ineffective and anti-CD59 was only slightly effective (18% mean cell lysis) in increasing the susceptibility of the lung cancer cell lines to complement, while the same antibodies were very effective in facilitating complement-mediated lysis of the normal nasal epithelial cells (50% mean cell lysis with CD59 MoAb). On the other hand, detachment of DAF and CD59 by phosphatidylinositol-specific phospholipase C (PIPLC) from the lung cancer cell lines abrogated their resistance to lysis. We suggest that the biology of cell membrane CIP molecules in human lung cancer cell lines is different from that of CIP in normal respiratory epithelial cells. Human lung cancer cell lines are able to prevent significant complement activation upon its cell membrane and are therefore especially resistant to complement-mediated lysis. Complement resistance may serve this common and highly lethal human cancer as an escape mechanism from the body's immunosurveillance and prevent effective immunotherapy with tumour-specific MoAbs.     

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.     

Decision-making process in abdominal surgery in the geriatric patient

The high rates of abdominal disorders in a growing population of geriatric patients and the greater willingness of the surgeon to cope with major problems in the elderly are factors contributing to a steady increase in abdominal procedures in this group. Four hundred consecutive major abdominal surgical procedures in patients over 70 years of age were submitted for computer analysis, the purpose of which was to determine the principal factors affecting mortality and morbidity. The etiological profile of abdominal surgery in the elderly was characterized by a high percentage of procedures related to the biliary tract, with the second largest group being those for intestinal obstruction due to benign and malignant conditions. The decision-making process in geriatric surgery is of great importance, requiring consideration of ethical, medico-legal and economic factors in addition to the purely medical ones. Analysis of data presented in this series leads to the following conclusions:

1. There is a declining mortality rate in all elective operations in the elderly, in the absence of widespread malignancy.
2. Timing is all important in abdominal emergencies in the elderly, and early operations are usually more successful than either immediate or delayed operations.
3. Definitive procedures are sometimes both safer and more cost effective than minimal procedures performed under such circumstances.
4. The principal factors leading to high mortality rates are the presence of malignancy, generalized peritonitis, and moderate-to-severe involvement of life-support systems.

     

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.     

VISUAL PATHWAY TUMORS AND HYDROCEPHALUS

The authors evaluated the impact of hydrocephalus on the clinical picture of children with visua pathway tumor (VPT) with or without neurofibromatosis (NF).Charts of children with VPT treated in the authors' center since 1985 were retrospectively reviewed, and those with hydrocephalus were selected and summarized. Thirty-five children with VPT were found, of whom 20 had NF.Hydrocephalus was found in 4 children with NF (20% ) and in 5 without NF (33.3% ). In 6 ofthechildren, ventricular dilatation with signs of acute increased intracranial pressure already existed at the time of diagnosis and the hydrocephalus was shunted at this time. In the other 3 children, all with NF,the hydrocephalus resulted from slowly developing aqueductal stenosis, leading in 2 to severe visual acuity deterioration. The results suggest that in children with VPT and NF, hydrocephalus, and especially hydrocephalus resulting from aqueductal stenosis, is more frequent than in the general population of NF patients, and less frequent than in VPT patients without NF. The possibility of the indolent development of hydrocephalus should be borne in mind while following children with NF. The optic nerve, when already involved with a glioma, is more vulnerable to increased pressure. Thus, in children with VPT and NF, any ventricular dilatation should lead to a consideration of early shunting.     

Seasonal Changes in the Incidence of Transient Global Amnesia

MethodsEvery patient with acute presentation of amnesia at our medical center is hospitalized for observation and evaluation. We reviewed the monthly occurrence of TGA in our patient population between 2000 and 2014, and compared this to non-TGA hospitalizations during the same time period.ResultsDuring the analysis period, 154 patients who met the criteria for TGA were hospitalized, as well as 259,007 non-TGA hospitalizations. The annual occurrence of TGA ranged from 5 to 16 hospitalizations. There were 91 TGA events in women and 63 in men, in subjects aged 62.8±10.6 years (mean±SD). The incidence was maximal during December [odds ratio (OR)=2.83, 95% confidence interval (CI)=1.20–6.67] and March (OR=2.77, 95% CI=1.17–6.56), and minimal from April to August. The incidence exhibited an increase followed by a decrease from October to February. A seasonal trend was observed as well, with incidence peaks occurring in winter (OR=1.82, 95% CI=1.12–2.96) and spring (OR=1.80, 95% CI=1.10–2.94).ConclusionsOur findings suggest that the incidence of TGA exhibits seasonal variations. This observation may help to improve the understanding of the pathophysiology underlying TGA.