Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism Modulates Reversible Cerebral Vasoconstriction Syndromes

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) could be complicated by cerebral ischemic events. Hypothetical mechanisms of RCVS involve endothelial dysfunction and sympathetic overactivity, both of which were reported to be related to brain-derived neurotrophic factor (BDNF). The study investigated the association between functional BDNF Val66Met polymorphism and RCVS. METHODS: Patients with RCVS and controls were prospectively recruited and genotyped for the BDNF Val66Met polymorphism. Magnetic resonance angiography (MRA) and transcranial color-coded Doppler sonography were employed to evaluate cerebral vasoconstriction. Genotyping results, clinical parameters, vasoconstriction scores, mean flow velocities of the middle cerebral artery (V(MCA)), and Lindegaard indices were analyzed. Split-sample approach was employed to internally validate the data. PRINCIPAL FINDINGS: Ninety Taiwanese patients with RCVS and 180 age- and gender-matched normal controls of the same ethnicity completed the study. The genotype frequencies did not differ between patients and controls. Compared to patients with Met/Met homozygosity, patients with Val allele had higher mean vasoconstriction scores of all arterial segments (1.60±0.72 vs. 0.87±0.39, p<0.001), V(MCA) values (116.7±36.2 vs. 82.7±17.9 cm/s, p<0.001), and LI (2.41±0.91 vs. 1.89±0.41, p = 0.001). None of the Met/Met homozygotes, but 38.9% of the Val carriers, had V(MCA) values of >120 cm/s (p<0.001). Split-sample validation by randomization, age, entry time or residence of patients demonstrated concordant findings. CONCLUSIONS: Our findings link BDNF Val66Met polymorphism with the severity of RCVS for the first time and implicate possible pathogenic mechanisms for vasoconstriction in RCVS

The Day-to-Day Impact of Urogenital Aging: Perspectives from Racially/Ethnically Diverse Women

Urogenital symptoms affect up to half of women after menopause, but their impact on women’s day-to-day functioning and wellbeing is poorly understood. Postmenopausal women aged 45 to 80 years reporting urogenital dryness, soreness, itching, or pain during sex were recruited to participate in in-depth focus groups to discuss the impact of their symptoms. Focus groups were homogenous with respect to race/ethnicity and stratified by age (for White or Black women) or language (for Latina women). Transcripts of sessions were analyzed according to grounded theory. Six focus groups were conducted, involving 44 women (16 White, 14 Black, 14 Latina). Five domains of functioning and wellbeing affected by symptoms were identified: sexual functioning, everyday activities, emotional wellbeing, body image, and interpersonal relations. For some participants, symptoms primarily affected their ability to have and enjoy sex, as well as be responsive to their partners. For others, symptoms interfered with everyday activities, such as exercising, toileting, or sleeping. Participants regarded their symptoms as a sign that they were getting old or their body was deteriorating; women also associated symptoms with a loss of womanhood or sexuality. Additionally, participants reported feeling depressed, embarrassed, and frustrated about their symptoms, and expressed reluctance to discuss them with friends, family, or health care providers. Urogenital symptoms can have a marked impact on sexual functioning, everyday activities, emotional wellbeing, body image, and interpersonal relations after menopause. Clinicians may need to question women actively about these symptoms, as many are reluctant to seek help for this problem

Small-Group Learning in an Upper-Level University Biology Class Enhances Academic Performance and Student Attitudes Toward Group Work

To improve science learning, science educators' teaching tools need to address two major criteria: teaching practice should mirror our current understanding of the learning process; and science teaching should reflect scientific practice. We designed a small-group learning (SGL) model for a fourth year university neurobiology course using these criteria and studied student achievement and attitude in five course sections encompassing the transition from individual work-based to SGL course design. All students completed daily quizzes/assignments involving analysis of scientific data and the development of scientific models. Students in individual work-based (Individualistic) sections usually worked independently on these assignments, whereas SGL students completed assignments in permanent groups of six. SGL students had significantly higher final exam grades than Individualistic students. The transition to the SGL model was marked by a notable increase in 10th percentile exam grade (Individualistic: 47.5%; Initial SGL: 60%; Refined SGL: 65%), suggesting SGL enhanced achievement among the least prepared students. We also studied student achievement on paired quizzes: quizzes were first completed individually and submitted, and then completed as a group and submitted. The group quiz grade was higher than the individual quiz grade of the highest achiever in each group over the term. All students – even term high achievers –could benefit from the SGL environment. Additionally, entrance and exit surveys demonstrated student attitudes toward SGL were more positive at the end of the Refined SGL course. We assert that SGL is uniquely-positioned to promote effective learning in the science classroom

Use of horseradish peroxidase for gene-directed enzyme prodrug therapy with paracetamol

Gene therapy is a potential method of treating cancer with a greater degree of targeting than conventional therapies. In addition, therapy can be directed towards cells within the tumour population that are traditionally resistant to current treatment schedules. Horseradish peroxidase (HRP) can oxidise paracetamol to N-acetyl-p-benzoquinoneimine via a one-electron pathway. Incubation of human cells expressing HRP with 0.5–10 mm paracetamol reduced clonogenic survival, but had little effect on control cells. A small increase in apoptosis was seen and a decrease in the number of cells undergoing mitosis, consistent with reports in hepatocytes using higher paracetamol concentrations. The cytotoxicity was also seen under conditions of severe hypoxia (catalyst induced anoxia), indicating that the HRP/paracetamol combination may be suitable for hypoxia-targeted gene therapy

Reduced expression of intercellular adhesion molecule-1 in ovarian adenocarcinomas

Ovarian adenocarcinomas develop as the result of multiple genetic and epigenetic changes in the precursor ovarian surface epithelial (OSE) cells which result in a malignant phenotype. We investigated changes in gene expression in ovarian adenocarcinoma using a cDNA array containing 588 known human genes. We found that intercellular adhesion molecule-1 (ICAM-1) was expressed at lower levels in the ovarian tumour cell lines OAW42, PEO1 and JAM than in the immortalised human ovarian surface epithelial cell line HOSE 17.1. Further investigation revealed ICAM-1 was expressed in the surface epithelium of normal ovaries and both mRNA and protein expression levels were reduced in the majority of ovarian adenocarcinoma cell lines and primary tumours. ICAM-1 expression was increased in 8/8 cell lines treated with the de novo methyltransferase inhibitor 5-aza-2′-deoxycytidine, indicating that methylation of CpG islands may play a role in the down-regulation of its expression in primary tumours. There was a significant association between patients whose tumours expressed ICAM-1 and survival (P= 0.03), suggesting that expression levels of ICAM-1 may have clinical relevance. © 2001 Cancer Research Campaig

Lateral specialization in unilateral spatial neglect : a cognitive robotics model

In this paper, we present the experimental results of an embodied cognitive robotic approach for modelling the human cognitive deficit known as unilateral spatial neglect (USN). To this end, we introduce an artificial neural network architecture designed and trained to control the spatial attentional focus of the iCub robotic platform. Like the human brain, the architecture is divided into two hemispheres and it incorporates bio-inspired plasticity mechanisms, which allow the development of the phenomenon of the specialization of the right hemisphere for spatial attention. In this study, we validate the model by replicating a previous experiment with human patients affected by the USN and numerical results show that the robot mimics the behaviours previously exhibited by humans. We also simulated recovery after the damage to compare the performance of each of the two hemispheres as additional validation of the model. Finally, we highlight some possible advantages of modelling cognitive dysfunctions of the human brain by means of robotic platforms, which can supplement traditional approaches for studying spatial impairments in humans

Eye movements and brain oscillations to symbolic safety signs with different comprehensibility

Background: The aim of this study was to investigate eye movements and brain oscillations to symbolic safety signs with different comprehensibility. Methods: Forty-two young adults participated in this study, and ten traffic symbols consisting of easy-to-comprehend and hard-to-comprehend signs were used as stimuli. During the sign comprehension test, real-time eye movements and spontaneous brain activity [electroencephalogram (EEG) data] were simultaneously recorded. Results: The comprehensibility level of symbolic traffic signs significantly affects eye movements and EEG spectral power. The harder to comprehend the sign is, the slower the blink rate, the larger the pupil diameter, and the longer the time to first fixation. Noticeable differences on EEG spectral power between easy-to-comprehend and hard-to-comprehend signs are observed in the prefrontal and visual cortex of the human brain. Conclusions: Sign comprehensibility has significant effects on real-time nonintrusive eye movements and brain oscillations. These findings demonstrate the potential to integrate physiological measures from eye movements and brain oscillations with existing evaluation methods in assessing the comprehensibility of symbolic safety signs.open

Effects of abciximab on key pattern of human coronary restenosis in vitro: impact of the SI/MPL-ratio

BACKGROUND: The significant reduction of angiographic restenosis rates in the ISAR-SWEET study (intracoronary stenting and antithrombotic regimen: is abciximab a superior way to eliminate elevated thrombotic risk in diabetes) raises the question of whether abciximab acts on clopidogrel-independent mechanisms in suppressing neointimal hyperplasia. The current study investigates the direct effect of abciximab on ICAM-1 expression, migration and proliferation. METHODS: ICAM-1: Part I of the study investigates in cytoflow studies the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on TNF-α induced expression of intercellular adhesion molecule 1 (ICAM-1). Migration: Part II of the study explored the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on migration of HCMSMC over a period of 24 h. Proliferation: Part III of the study investigated the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on proliferation of HUVEC, HCAEC, and HCMSMC after an incubation period of 5 days. RESULTS: ICAM-1: In human venous endothelial cells (HUVEC), human coronary endothelial cells (HCAEC) and human coronary medial smooth muscle cells (HCMSMC) no inhibitory or stimulatory effect on expression of ICAM-1 was detected. Migration: After incubation of HCMSMC with abciximab in concentrations of 0.0002 – 2 μg/ml a stimulatory effect on cell migration was detected, statistical significance was achieved after incubation with 0.002 μg/ml (p < 0.05), 0.002 μg/ml (p < 0.001), and 0.2 μg/ml (p < 0.05). Proliferation: Small but statistically significant antiproliferative effects of abciximab were detected after incubation of HUVEC (0.02 and 2.0 μg/ml; p = 0.01 and p < 0.01), HCAEC (2.0 and 20.0 μg/ml; p < 0.05 and p < 0,01), and HCMSMC (2.0 and 20.0 μg/ml; p < 0.05 and p < 0.05). The significant inhibition (SI) of cell proliferation found in HCAEC and HCMSMC was achieved with drug concentrations more than 10 times beyond the maximal plasma level (MPL), resulting in a SI/MPL-ratio > 1. CONCLUSION: Thus, the anti-restenotic effects of systemically administered abciximab reported in the ISAR-SWEET-study were not caused by a direct inhibitory effect on ICAM-1 expression, migration or proliferation