Dementia prevention: Shared questions for research and clinical management

The emergence of advanced genetic technologies raises many challenges for dementia care and the conduct of related social, behavioural and clinical research. Genetic tests are already used to identify possible participants in dementia prevention trials. These tests are unlike any other in clinical medicine as they have the capacity to predict disease onset after intervals of many years with implications for other family members. Genetic counselling professionals support services in paediatrics, cancer diagnosis and some adult-onset diseases. Their capacity cannot meet the needs for pre- and post-test support of the many “at-risk” families living with late onset dementia. Most dementias are common, complex conditions in which multiple genetic and environmental factors play important and potentially modifiable roles. Large scale prevention studies are needed to test the effectiveness of interventions. Some economy of effort will be achieved by the preferential inclusion of “at-risk” families. Many such families are in contact with dementia care services and will be motivated to participate in prevention studies. However, practice standards and consensus-based guidelines do not yet exist. Support services are not available on a scale sufficient to prevent harm when risk is poorly communicated causing unnecessary psychological morbidity in unaffected family members. There is a pressing need for research to inform the development of study guidelines and to identify how services are strengthened to support these families during and after their participation in trials. Discourse analysis provides a useful method to collect and analyse data of this type and supports the conclusions of this review.     

A rapid,reliable, and inexpensive method for detection of di- and trinucleotide repeat markers and disease loci from dried blood spots

We used a rapid and inexpensive method for studying the FMR1 CGG-repeat from dried blood spots, prepared from heel pricks, finger pricks, or an aliquot of blood from a venipuncture. The procedure includes a single tube for preparation of template DNA for PCR and minimal handling, avoiding opportunities for mislabelling specimens and loss of template. We extended the protocol to numerous di- and trinucleotide repeat markers and disease loci, including FRAXE, FRAXF, DXS548, DRPLA, and ZFY. The use of a highly reliable and very inexpensive method which employs blood spots as a source for target DNA means that newborn Guthrie cards can be used to establish allele frequencies for linkage disequilibrium studies, that large populations can be screened for genetic disorders, and that mapping studies can proceed rapidly even when only small amounts of blood are available from key family members. © 1996 Wiley-Liss, Inc.     

Stress exposure among mexican americans and non-hispanic whites

In this article we examine differences between Mexican Americans and non-Hispanic Whites, and between U.S.- and Mexico-born Mexican Americans, in exposure to two sources of stress: life events and ongoing strains. Data were obtained from a survey of 1,244 Mexican-American and 1,149 non- Hispanic White randomly selected community residents. There were few ethnic differences in life events, although non-Hispanic Whites were more likely to report desirable or ambiguous events. Mexican-American immigrants were less likely than their U.S.-born counterparts to report most events. In contrast, Mexican Americans, especially immigrants, reported greater ongoing strain than non-Hispanic Whites. Different kinds of life events were associated with each type of strain.     

Invasive Breast Carcinoma with Neuroendocrine Differentiation: A Single-Center Analysis of Clinical Features and Prognosis

Introduction Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation. Patients Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records. Results Median age at the time of diagnosis was 61 years. 70% of patients had T2 – 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%. Conclusions Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases. Key words: neuroendocrine neoplasia of the breast, invasive breast cancer with neuroendocrine differentiation, neuroendocrine breast cancer, neuroendocrine markers, somatostatin receptor 2A     

Long-term effects of trauma: Post-traumatic stress among civilian internees of the japanese during world war II

This study examined predictors and health-related effects of post-traumatic stress among 129 civilian internees of the Japanese during World War II. Post-traumatic stress disorder was noted in 36.7% within the 6 months after their release and in 15.0% within the most recent 6 months. Women were more likely than men to indicate post-traumatic stress disorder within the 6 months after their release. Higher incomes were associated with lower levels of post-traumatic stress within the most recent 6 months. After controlling for demographic and internment-related factors, higher levels of post-traumatic stress were associated with poorer physical health. This association was stronger among older internees than among their younger counterparts. Implications of the findings for clinical gerontology are discussed.     

Tractostorm 2: Optimizing tractography dissection reproducibility with segmentation protocol dissemination

The segmentation of brain structures is a key component of many neuroimaging studies. Consistent anatomical definitions are crucial to ensure consensus on the position and shape of brain structures, but segmentations are prone to variation in their interpretation and execution. White‐matter (WM) pathways are global structures of the brain defined by local landmarks, which leads to anatomical definitions being difficult to convey, learn, or teach. Moreover, the complex shape of WM pathways and their representation using tractography (streamlines) make the design and evaluation of dissection protocols difficult and time‐consuming. The first iteration of Tractostorm quantified the variability of a pyramidal tract dissection protocol and compared results between experts in neuroanatomy and nonexperts. Despite virtual dissection being used for decades, in‐depth investigations of how learning or practicing such protocols impact dissection results are nonexistent. To begin to fill the gap, we evaluate an online educational tractography course and investigate the impact learning and practicing a dissection protocol has on interrater (groupwise) reproducibility. To generate the required data to quantify reproducibility across raters and time, 20 independent raters performed dissections of three bundles of interest on five Human Connectome Project subjects, each with four timepoints. Our investigation shows that the dissection protocol in conjunction with an online course achieves a high level of reproducibility (between 0.85 and 0.90 for the voxel‐based Dice score) for the three bundles of interest and remains stable over time (repetition of the protocol). Suggesting that once raters are familiar with the software and tasks at hand, their interpretation and execution at the group level do not drastically vary. When compared to previous work that used a different method of communication for the protocol, our results show that incorporating a virtual educational session increased reproducibility. Insights from this work may be used to improve the future design of WM pathway dissection protocols and to further inform neuroanatomical definitions.