Regional differentiation of cell densities in the left and right hippocampi of epileptic patients

Neuronal cell densities in surgically removed left or right hippocampal tissue of epileptic patients suffering from temporal lobe epilepsy were determined in CA1, CA4, and the dentate gyrus (DG). Mean densities showed no statistically significant left-right asymmetry in CA1 and the DG, consistent with findings by others. Mean densities did show previously unreported asymmetry in CA4; densities were significantly lower in the right CA4 than in the left. Another new finding is an asymmetry in regional intercorrelations: positive and significant correlations among the three subfields were obtained only in the left hippocampus. In addition, we confirmed previous findings of positive correlation between neuronal densities in CA1 and age of onset of habitual epilepsy, on either side. Taken together, the results suggest subtle left-right asymmetries in the vulnerability of the hippocampi to epilepsy-associated damage and/or higher neuronal connectivity or interdependence on the left than on the right.     

Evolution of the Simulated Data Problem

The simulated data problem was designed via an interactive process by the Simulation Problem Organizing Committee and the selected data simulators. Based on discussions at the previous Genetic Analysis Workshop, many of the features of previous simulation problems, such as a complex disease, genome scan, and replication, were retained and in addition, a population genetics model was used to generate the simulated genes. We describe the process that was used to structure the problem and summarize the discussions about many of the scientific issues that were considered. © 2001 Wiley‐Liss, Inc.     

Laparoscopy versus laparotomy for detorsion and sparing of twisted ischemic adnexa.

BACKGROUND: Torsion of the ovary is an urgent event for fertile women. Until recent years, the common treatment for twisted ischemic ovaries was salpingo-oophorectomy. We have demonstrated in the past that the ovary can be salvaged provided detorsion is performed. We studied the outcome of women undergoing minimal surgery for ischemic ovaries versus the extended procedure including cystectomy in respect of ovarian function and fertility performance. METHODS: We retrospectively studied 102 women who underwent surgery for torsion of the ovary in which the macroscopic appearance of black-bluish ischemic adnexa was encountered during surgery. Detorsion without removal of the adnexa or the ovary was performed by laparoscopy in 67 patients and by laparotomy in 35 patients. Patients' files were reviewed for immediate and late outcomes. Patients were examined postoperatively with vaginal ultrasound for ovarian follicular function. Data concerning patients' further surgeries or in vitro fertilization were retrieved from the charts as well. RESULTS: Febrile morbidity was approximately 15% and 29% in the laparoscopy and laparotomy groups, respectively. Hospital stay was 2.1 +/- 1.2 and 7.4 +/- 1.5 days in the laparoscopy and laparotomy groups, respectively (P<0.001). Ultrasound follow-up was available in 60 of 67 patients who underwent laparoscopy and in 32 of 35 patients treated by laparotomy. Normal-sized ovaries with follicular development were encountered in the detorsed side in 93% and 91%, respectively. Normal macroscopic appearance of the adnexa at subsequent surgeries was reported in 9 of 9 patients in the laparoscopy group and in 4 of 5 patients in the laparotomy group. Four patients from the laparoscopy group and 2 from the laparotomy group underwent subsequent in vitro fertilization. In all 6 patients, oocytes retrieved from the previously detorsed ovary were fertilized. In both groups, none of the patients developed clinical signs of pelvic or systemic thromboembolism. CONCLUSIONS: Torsion of the ischemic adnexa should be treated laparoscopically by detorsion and adnexal sparing.     

Serotonin transporter polymorphism and bleeding time during SSRI therapy

AIMS

Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine, are associated with an increased risk of bleeding disorders, probably due to decreased platelet serotonin levels. Polymorphisms in the serotonin transporter gene (5-HTT) may influence the risk of SSRI-induced bleedings. The aim of this study was to investigate whether and to what extent the serotonin transporter polymorphism increases the bleeding time in paroxetine users.

METHODS

A prospective study, using routinely collected hospital and pharmacy data, was conducted among 43 patients between 18 and 70 years old and on >4 weeks of paroxetine therapy. The genotype for the serotonin transporter (5-HTTLPR), trough paroxetine levels, platelet function analyser (PFA)-closure time (collagen/epinephrine) and a complete blood count were assessed.

RESULTS

No significant difference was seen between the SS, SL, LL genotypes of the serotonin transporter and the PFA-closure time. None of the covariates had a significant influence on the association between the serotonin transporter polymorphism and the PFA-closure time. Age and von Willebrand factor showed the largest contribution, but not significant. No difference was seen between the PFA-closure time and the frequency of bruising and spontaneous bleedings between patients with at least one S allele and with the LL genotype.

CONCLUSION

Our prospective study does not support the assumption that paroxetine can cause a prolonged PFA-closure time during paroxetine therapy due to a serotonin transporter polymorphism. Old age, use of platelet inhibitors and a history of gastrointestinal bleeding remain the focus for SSRI-induced bleeding complications.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• From case reports it has become clear that selective serotonin reuptake inhibitors (SSRIs) can cause bleeding disorders.
• The causative mechanism is as yet unknown.
• Several publications have described the relationship between the serotonin transporter genotype and the prevalence of certain diseases such as depression, but few have focused on the relationship with side-effects of antidepressive drugs such as SSRIs.

WHAT THIS STUDY ADDS

• This study suggests that the association between SSRI therapy and prolonged bleeding time may not be related to the polymorphism of the serotonin transporter (5-HTTLPR) investigated.

     

Can technology help close the gender gap in literacy achievement? Evidence from boys and girls sharing eBooks

Abstract

Purpose: Digital technologies may offer new solutions to old problems or bring additional complications. In this paper, we address a longstanding and widespread issue, specifically, slower acquisition of literacy skills by boys compared to girls. Electronic books might serve to close this gender gap because it is believed that boys are generally less motivated to read but that boys are especially engaged by technology. However, interactive features in electronic books could further challenge boys’ weak self-regulation skills, thus impeding their literacy achievement. Gender differences in literacy learning and the learning environment were examined in two studies conducted in French-language kindergartens.

Method: Study 1 involved 56 girls and 36 boys, where the relationship between oral language precursors at school entry and literacy outcomes at the end of second grade was assessed. Study 2 included 43 girls and 44 boys, where interactions between children and an adult during shared reading exchanges with electronic books were coded to reveal gender-related differences in the learning environment.

Result: In Study 1, the oral language and emergent literacy screener in first grade significantly predicted second grade spelling, with a significant gender gap in orthographic skills favouring girls in grade two despite similar oral language skills in grade one. In Study 2, adult readers were observed to re-direct boys’ attention or regulate their behaviour more often during shared reading (when compared to girls).

Conclusion: These findings suggest that self-regulation may mediate early reading precursors and different literacy outcomes by gender. Strategies to alleviate stress and improve the learning environment during literacy activities are suggested. Overall, it is clear that technology is neither beneficial nor harmful by itself; rather, synchronised interactions between adult, child and technological features are crucial. Furthermore, the broader social context in which teaching and learning interactions are embedded plays a role.     

Satisfaction and perceptions of long-term manual wheelchair users with a spinal cord injury upon completion of a locomotor training program with an overground robotic exoskeleton

Aim: The main objectives of this study were to quantify clients’ satisfaction and perception upon completion of a locomotor training program with an overground robotic exoskeleton.

Methods: A group of 14 wheelchair users with a spinal cord injury, who finished a 6–8-week locomotor training program with the robotic exoskeleton (18 training sessions), were invited to complete a web-based electronic questionnaire. This questionnaire encompassed 41 statements organized around seven key domains: overall satisfaction related to the training program, satisfaction related to the overground robotic exoskeleton, satisfaction related to the program attributes, perceived learnability, perceived health benefits and risks and perceived motivation to engage in physical activity. Each statement was rated using a visual analogue scale ranging from “0?=?totally disagree” to “100?=?completely agree”.

Results: Overall, respondents unanimously considered themselves satisfied with the locomotor training program with the robotic exoskeleton (95.7?±?0.7%) and provided positive feedback about the robotic exoskeleton itself (82.3?±?6.9%), the attributes of the locomotor training program (84.5?±?6.9%) and their ability to learn to perform sit–stand transfers and walk with the robotic exoskeleton (79.6?±?17%). Respondents perceived some health benefits (67.9?±?16.7%) and have reported no fear of developing secondary complications or of potential risk for themselves linked to the use of the robotic exoskeleton (16.7?±?8.2%). At the end of the program, respondents felt motivated to engage in a regular physical activity program (91.3?±?0.1%).

Conclusion: This study provides new insights on satisfaction and perceptions of wheelchair users while also confirming the relevance to continue to improve such technologies, and informing the development of future clinical trials.

• Implications for Rehabilitation

• All long-term manual wheelchair users with a spinal cord injury who participated in the study are unanimously satisfied upon completion of a 6–8-week locomotor training program with the robotic exoskeleton and would recommend the program to their peers.

• All long-term manual wheelchair users with a spinal cord injury who participated in the study offered positive feedback about the robotic exoskeleton itself and feel it is easy to learn to perform sit–stand transfers and walk with the robotic exoskeleton.

• All long-term manual wheelchair users with a spinal cord injury who participated in the study predominantly perceived improvements in their overall health status, upper limb strength and endurance as well as in their sleep and psychological well-being upon completion of a 6–8-week locomotor training program with the robotic exoskeleton.

• All long-term manual wheelchair users with a spinal cord injury who participated in the study unanimously felt motivated to engage in a regular physical activity program adapted to their condition and most of them do plan to continue to participate in moderate-to-strenuous physical exercise.

• Additional research on clients’ perspectives, especially satisfaction with the overground exoskeleton and locomotor training program attributes, is needed.

     

Trends in statin therapy initiation during the period 2000–2010 in Israel

Purpose

The aim of this population-based study is to describe trends in the characteristics and treatment patterns of statin initiators over the first decade of the 21st century.

Methods

New statin use was studied retrospectively using the database of Maccabi Healthcare Services (MHS), a large Israeli health maintenance organization. Statin initiators were defined as MHS members aged ≥30 years who first purchased statins between 2000 and 2010. The starting dose was calculated in simvastatin equivalents based on the World Health Organization’s daily defined dose index. Persistence was calculated as the percentage of days covered (PDC) with statins during the first year of therapy.

Results

Statin initiation peaked in 2005 and decreased from 38.6 to 18.6 per 1,000 in the period 2005–2010. The average age at therapy initiation decreased from 58.9 (±12.0) to 54.5 (±11.7) years, and the average (SD) baseline low-density lipoprotein cholesterol (LDL-C) decreased from 4.2 (±1.1) to 4.0 (±0.9) mmol/l during the study period. Women were on average 3 years older than men at treatment initiation, with a higher baseline LDL-C. Among statin initiators, the prevalence of ischemic heart disease (IHD) decreased from 17.8 to 6.7 %, and diabetes prevalence increased from 8.6 to 15.7 %, peaking in 2008 (18.0 %). The PDC with statins ranged between 52.9 and 57.7 %. Simvastatin use at initiation increased from 27.5 % in 2000 to >90 % since 2002. Starting dose increased from 18.5 (±8.9) to 24.3 (±13.7) mg simvastatin equivalent.

Conclusions

Among the study population, statin initiators were increasingly characterized by a lower cardiovascular risk—namely, younger individuals without IHD and with a lower baseline LDL-C. These trends underscore the important shift towards statin initiation for primary prevention, as well as the need to balance between benefits and the potential side effect of statins.     

Characterization of canine osteosarcoma by array comparative genomic hybridization and RT-qPCR: signatures of genomic imbalance in canine osteosarcoma parallel the human counterpart

Osteosarcoma (OS) is the most commonly diagnosed malignant bone tumor in humans and dogs, characterized in both species by extremely complex karyotypes exhibiting high frequencies of genomic imbalance. Evaluation of genomic signatures in human OS using array comparative genomic hybridization (aCGH) has assisted in uncovering genetic mechanisms that result in disease phenotype. Previous low-resolution (10-20 Mb) aCGH analysis of canine OS identified a wide range of recurrent DNA copy number aberrations, indicating extensive genomic instability. In this study, we profiled 123 canine OS tumors by 1 Mb-resolution aCGH to generate a dataset for direct comparison with current data for human OS, concluding that several high frequency aberrations in canine and human OS are orthologous. To ensure complete coverage of gene annotation, we identified the human refseq genes that map to these orthologous aberrant dog regions and found several candidate genes warranting evaluation for OS involvement. Specifically, subsequenct FISH and qRT-PCR analysis of RUNX2, TUSC3, and PTEN indicated that expression levels correlated with genomic copy number status, showcasing RUNX2 as an OS associated gene and TUSC3 as a possible tumor suppressor candidate. Together these data demonstrate the ability of genomic comparative oncology to identify genetic abberations which may be important for OS progression. Large scale screening of genomic imbalance in canine OS further validates the use of the dog as a suitable model for human cancers, supporting the idea that dysregulation discovered in canine cancers will provide an avenue for complementary study in human counterparts.     

Arthritis augments breast cancer metastasis: role of mast cells and SCF/c-Kit signaling

Introduction

Breast cancer remains the second leading cause of cancer-related deaths for women in the United States. Metastasis is regulated not only by intrinsic genetic changes in malignant cells, but also by the microenvironment, especially those associated with chronic inflammation. We recently reported that mice with autoimmune arthritis have significantly increased incidence of bone and lung metastasis and decreased survival associated with breast cancer. In this study, we evaluated the mechanism underlying the increased metastasis.

Methods

We used two mouse models; one that develops spontaneous autoimmune arthritis (SKG mice) injected with metastatic breast cancer cells (4T1), and another that develops spontaneous breast cancer (MMTV-PyV MT mice) injected with type II collagen to induce autoimmune arthritis. Mast cell levels and metastasis were monitored.

Results

First, we confirmed that breast tumor-bearing arthritic mice have a significantly higher incidence of bone and lung metastasis than do their nonarthritic counterparts. Next, we showed increased recruitment of mast cells within the primary tumor of arthritic mice, which facilitates metastasis. Next, we report that arthritic mice without any tumors have higher numbers of mast cells in the bones and lungs, which may be the underlying cause for the enhanced lung and bone metastases observed in the arthritic mice. Next, we showed that once the tumor cells populate the metastatic niches (bones and lungs), they further increase the mast cell population within the niche and assist in enhancing metastasis. This may primarily be due to the interaction of c-Kit receptor present on mast cells and stem cell factor (SCF, the ligand for ckit) expressed on tumor cells. Finally, we showed that targeting the SCF/cKit interaction with an anti-ckit antibody reduces the differentiation of mast cells and consequently reduces metastasis.

Conclusion

This is the first report to show that mast cells may play a critical role in remodeling not only the tumor microenvironment but also the metastatic niche to facilitate efficient metastasis through SCF/cKit interaction in breast cancer with arthritis.