Neuroimaging in Pineal Tumors

BACKGROUND AND PURPOSE: The authors report radiological findings in 11 tumors in the pineal region, which were histologically diagnosed as germinomas, pineocytomas pineoblastomas, ependymomas, teratomas, and astrocytomas. METHODS: Computed tomography (CT) was performed in seven patients and magnetic resonance imaging (MRI) was performed in all patients. RESULTS: CT showed a solid or solid/cystic mass with variable contrast enhancement. MRI showed a heterogeneous mass, with hypointense signal on T1 and iso/hyperintense signal on T2-weighted images (WI) and gadolinium enhancement. Extension to adjacent structures occurred in five patients and spread through the cerebral spinal fluid (CSF) in two. CONCLUSIONS: Pineal region tumors have no pathognomonic imaging pattern. MRI and CT are complementary in diagnosis and are important to determine localization, extension, and meningeal spread.     

Neighbourhood differences in diet: the Atherosclerosis Risk in Communities (ARIC) Study

STUDY OBJECTIVE: To investigate whether neighbourhood characteristics are related to dietary patterns independently of individual level variables. DESIGN: A cross sectional analysis of the relation between neighbourhood median household income and food and nutrient intakes, before and after adjustment for individual level variables. SETTING: Four United States communities (Washington Co, MD; Suburban Minneapolis, MN; Forsyth Co, NC, and Jackson, MS). PARTICIPANTS: 13,095 adults aged 45 to 64 years participating in the baseline examination of the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study of atherosclerosis. MEASUREMENTS AND MAIN RESULTS: Information on diet and individual level income was obtained from the baseline examination of the ARIC Study. Diet was assessed using a semi-quantitative food frequency questionnaire. Information on neighbourhood (census defined block groups) median household income was obtained from the 1990 US Census. Multilevel models were used to account for the multilevel structure of the data. Living in lower income neighbourhoods was generally associated with decreased energy adjusted intake of fruits, vegetables, fish, and increased intake of meat. Patterns generally persisted after adjustment for individual level income, but were often not statistically significant. Inconsistent associations were recorded for the intake of saturated fat, polyunsaturated fat, and cholesterol. Overall, individual level income was a more consistent predictor of diet than neighbourhood income. CONCLUSION: Despite limitations in the definition and characterisation of neighbourhoods, this study found consistent (albeit small) differences across neighbourhoods in food intake, suggesting that more in depth research into potential neighbourhood level determinants of diet is warranted.     

Labial Adhesion with Acute Urinary Retention Secondary to Bartholin's Abscess

Labial adhesions are usually seen in early childhood or in the postmenopausal years, but this clinical entity is rarely seen in the reproductive years. We report a case of labial adhesion with acute urinary retention secondary to Bartholin's abscess in a reproductive‐aged woman with normal menstrual periods. We emphasize the possible occurrence of labial adhesion following Bartholin's abscess in the reproductive years with normal estrogen levels.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA

Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state.     

Examining the Impact of the Walking School Bus With an Agent-Based Model

We used an agent-based model to examine the impact of the walking school bus (WSB) on children’s active travel to school. We identified a synergistic effect of the WSB with other intervention components such as an educational campaign designed to improve attitudes toward active travel to school. Results suggest that to maximize active travel to school, children should arrive on time at “bus stops” to allow faster WSB walking speeds. We also illustrate how an agent-based model can be used to identify the location of routes maximizing the effects of the WSB on active travel. Agent-based models can be used to examine plausible effects of the WSB on active travel to school under various conditions and to identify ways of implementing the WSB that maximize its effectiveness.Active travel to school (ATS) is of special significance to children’s physical and mental health and has important implications for the environment and sustainable development.1,2 Today, fewer than 15% of US children and adolescents walk or bicycle to school, compared with approximately 50% half a century ago.3 Multiple factors are associated with ATS, including characteristics of children and families as well as features of schools and neighborhoods.1,4Existing interventions designed to promote ATS are heterogeneous in terms of size, scope, and focus,5–7 and according to a recent systematic review,8 most have shown limited effectiveness in promoting ATS. Interventions targeting schools, parents, and communities and those geared toward a specific goal tend to be more effective than those that are broader in focus. The ability to evaluate an intervention’s impact has often been limited by methodological issues such as lack of an experimental study design and limitations in the validity and reliability of the measures used. The complexity of the factors influencing ATS and the fact that the effects of these factors may vary from context to context further limit the utility of both observational and experimental studies in evaluating the long-term impact of various interventions.One notable example of an intervention to increase ATS is the walking school bus (WSB).9 The WSB is a program in which children walk to school in groups led by adults along a planned route with designated meeting places (i.e., “bus stops”) where other children join in. The primary goal is to allow children to actively and safely commute to school. During the 2009–2010 school year, about 6.2% of the elementary schools in the United States organized a WSB.10 Although most WSBs have shown promising short-term benefits,7,11–15 evidence of their effectiveness over long periods is limited.A major challenge in evaluating the impact of interventions such as the WSB is that it is difficult to evaluate how the intervention may interact with features of the context in which it is implemented or how features of the intervention may influence its effectiveness. For example, the effects of ATS may be modified by educational campaigns targeted at increasing favorable attitudes toward walking among children.Various features related to how the WSB is implemented may also influence its effectiveness. When using the WSB, children may take longer to arrive at school because of the waiting time at the “bus stop,” the group’s decreased walking speed, and detours that need to be taken for the child to reach the WSB route. If children arrive at the stop earlier (increasing their waiting times), group walking speed can increase (because the group is less likely to wait at each stop for other children to join in), reducing the total travel time. The challenge is to find the strategy that minimizes waiting time while maximizing walking speed.Another challenge for the WSB is the selection of bus routes and stops. More bus routes may attract more children to join the WSB but may also necessitate more adult involvement. It is therefore important to identify the most beneficial placement of a limited number of bus routes. To our knowledge, there is scant information on how these contextual or implementation factors could affect the impact of the WSB on children’s active travel to school.A large body of work has recommended multilevel interventions (i.e., interventions that combine environmental and individual-level elements) for behavioral change because of possible synergistic effects.16–20 It has been noted that evidence on interventions derived from randomized trials is often limited because the impact of context as a modifier cannot be investigated. For example, it is well established that physical activity is influenced by the interplay between environmental and psychological factors.21,22 Yet, existing observational or experimental studies are ill suited to investigate these interactions. Modeling or simulation studies can be important sources of complementary evidence on how the impact of interventions such as the WSB may be affected by various contextual factors.In public health, there has been growing interest in using complex systems modeling as a complement to observational studies and randomized trials to better understand the plausible impact of interventions or policies in different contexts.23–25 The tools of complex systems models allow researchers to evaluate the effects of interventions while accounting for dependencies and feedbacks, which are not easily captured in standard statistical analyses. One such tool is agent-based modeling. Agent-based models (ABMs) are computational models that can be used to simulate the actions and interactions of agents as well as the dynamic interactions between agents and their environments to gain an understanding of the functioning of a system.26,27 ABMs have increasingly been used to investigate how the social and built environments shape people’s travel behavior.28–32We previously developed an ABM31 to simulate children’s ATS within a hypothetical city. The model was used to explore the plausible implications of policies targeting 2 established barriers to ATS: long distance to school and traffic safety. In this study, we extended the model to examine the potential effects of the WSB on ATS. Specifically, we examined whether the effects of the WSB are enhanced by an educational campaign aimed at improving attitudes toward ATS among children, how changing the walking speed of the WSB and the waiting time for children at the WSB stops affects ATS, and the impact of different bus route placements. All 3 issues are important in the design and implementation of the WSB but are difficult to assess in experimental or observational studies. Because previous work suggested that ATS is influenced by population density,31 we investigated the 3 issues across various levels of population density.