Occult Breast Carcinoma Presenting as Gastrointestinal Metastases

Occult breast cancer has frequently been described as presenting as axillary lymph node metastases but rarely as gastrointestinal metastases, Varadarajan et al. (2007). In extremely rare situations, cancerous lesions identified in the gastrointestinal tract have been determined to be metastatic lesions from primary breast cancers, Taal et al. (2000). We report a case of an occult lobular adenocarcinoma presenting as gastrointestinal metastases. It is essential that the possibility of lesions found in the gastrointestinal tract originating from distant or occult cancers be considered in order that appropriate therapeutic options may be discussed and considered early after diagnosis

Investigation through neutron experimentation and crystal field calculation into the connectivity of multiferroic DyMnO3 and antiferromagnetic R = [Dy, Tb, Nd, Ce]

Multiferroic materials that have a unique coupling of magnetic and electronic degrees of freedom are possible candidates for the next generation of data storage and data transfer technology. For this thesis we performed inelastic neutron scattering on an oxygen isotopically substituted sample DyMnO3. This was done in order to better understand the structural and magnetic interaction in these materials, and in an attempt to improve the magnetic signal for better performance in applications. A comparison between DyMnO3, and also multiferroic TbMnO3 to the isostructural antiferromagnetic series RVO3 R = [Tb, Ce, Dy, Nd] is carried out in order to better understand the complex correlations in the multiferroic materials. Inelastic neutron scattering experiments were performed on TbVO3, CeVO3 and DyMnO3 and results from previously performed experiments on DyVO3, NdVO3 and TbMnO3 were compared to the crystal field excitation calculations. Crystal field excitation calculations used the point charge ionic model, and were found to predict the experimental crystal field excitations, with a deviation of 0.5 meV. In TbVO3 and CeVO3 the interaction between the molecular field and the crystal field excitations is confirmed. Moreover, the point charge ionic model was found to accurately predict the properties of the crystal field excitations for the strongly correlated electron systems: RMnO3 multiferroics and the RVO3 antiferromagnetic vanadates

Normal-appearing white matter in multiple sclerosis is in a subtle balance between inflammation and neuroprotection

Multiple sclerosis is a chronic inflammatory disease of the CNS. Although progressive axonal injury and diffuse inflammatory damage has been shown in the chronic phase of the disease, little is known about the molecular mechanisms underlying these pathological processes. In order to identify these mechanisms, we have studied the gene expression profile in non-lesion containing tissue, the so-called normal-appearing white matter (NAWM). We performed differential gene expression analysis and quantitative RT-PCR on subcortical white matter from 11 multiple sclerosis and 8 control cases. Differentially expressed genes were further analysed in detail by in situ hybridization and immunofluorescence studies. We show that genes known to be involved in anti-inflammatory and protective mechanisms such as STAT6, JAK1, IL-4R, IL-10, Chromogranin C and Hif-1α are consistently upregulated in the multiple sclerosis NAWM. On the other hand, genes involved in pro-inflammatory mechanisms, such as STAT4, IL-1β and MCSF, were also upregulated but less regularly. Immunofluorescence colocalization analysis revealed expression of STAT6, JAK1, IL-4R and IL-13R mainly in oligodendrocytes, whereas STAT4 expression was detected predominantly in microglia. In line with these data, in situ hybridization analysis showed an increased expression in multiple sclerosis NAWM of HIF-1α in oligodendrocytes and HLA-DRα in microglia cells. The consistency of the expression levels of STAT6, JAK1, JAK3 and IL-4R between the multiple sclerosis cases suggests an overall activation of the STAT6-signalling pathway in oligodendrocytes, whereas the expression of STAT4 and HLA-DRα indicates the activation of pro-inflammatory pathways in microglia. The upregulation of genes involved in anti-inflammatory mechanisms driven by oligodendrocytes may protect the CNS environment and thus limit lesion formation, whereas the activation of pro-inflammatory mechanisms in microglia may favour disease progression. Altogether, our data suggests an endogenous inflammatory reaction throughout the whole white matter of multiple sclerosis brain, in which oligodendrocytes actively participate. This reaction might further influence and to some extent facilitate lesion formatio

Resolving Relationships at the Animal-Fungal Divergence: A Molecular Phylogenetic Approach for Understanding the Ecology and Evolution of the Protist Trichomycetes

The Ichthyosporea (= Mesomycetozoea) is a relatively understudied class of unicellular symbionts that molecular phylogenies have placed at the divergence of animals and fungi. Subsumed in this class are the cosmopolitan families Eccrinidae and Amoebidiidae (referred to as “protist trichos” or “trichos” herein), which are considered obligate commensal endobionts of various arthropods, including marine, freshwater and terrestrial hosts. Once thought to be members of the fungal class Trichomycetes due to their hyphal-like growth form and ecological similarity, molecular evidence has necessitated reclassification. However, evolutionary relationships within and between them are still unclear as the number of taxa sampled and/or the amount of gene data gathered have been factors limiting resolution. These organisms are also taxonomically challenging since informative, homologous morphological characters are difficult to discern using only a light microscope (the method by which members of Amoebidiidae and Eccrinidae have traditionally been described), and only a few have been obtained in axenic culture. Most protist trichos reported thus far lack sufficiently detailed morphological parameters to permit ease and confidence in species identification. As such, relatively little is known about the ecology and biology of most members, some of which were originally classified as fungi or algae. As new members were discovered or reclassified, two orders were established: Dermocystida and Eccrinida. Whereas members of the Dermocystida are almost entirely parasites of various metazoan hosts, only three clades within the Eccrinida contain known parasites, with the remaining members regarded as commensalistic. Interestingly, the putative closest extant relative to both groups is Ichthyophonus, an economically relevant fish parasite, which can invade vital host tissues (e.g. heart and liver) via circulating amoeba-like cells,causing disease and potentially death. The most recent molecular systematic study of the protist trichos was published about a decade ago, and there is as yet but one Paramoebidium (Amoebidiidae) sequence deposited in GenBank. Currently, based on molecular data, the Amoebidiidae are supported as monophyletic (based on one sample from each of its two genera) while the monophyly of the Eccrinidae is indicated, but not supported. Likewise, the relationship of the protist trichos to Ichthyophonus remains unresolved. As such, the first chapter of this thesis addressed the molecular phylogeny of order Eccrinida, with particular emphasis on the protist trichos by first amplifying and sequencing rDNA genes (18S and 28S) for over 100 new samples. Amplification tests were also attempted for several protein-coding genes, including heat shock protein 70. The resulting tree inferences were used in subsequent analyses of ecological and life history traits via ancestral state reconstructions and Bayesian tip-association significance testing (BaTS). In the second chapter, samples of Paramoebidium spp. were morphologically and molecularly assessed as a case study into the utility of traditionally described morphological characters for taxonomic delimitation among protist trichos. Morphological differentiation of Paramoebidium spp. has been notoriously problematic due to inter- and intraspecific variability. Host specificity within the genus was early suggested, but later questioned, and has not been subjected to thorough evaluation. Therefore, host and hyphal characters were analyzed via three different methods of ancestral state reconstruction, as well as with BaTS on a molecular phylogeny of over 70 Amoebidiidae samples. Results of these studies indicate: 1) contrary to previous hypotheses, the Amoebidiidae may be paraphyletic, 2) relationships among Eccrinidae and between the protist trichos and Ichthyophonus remain unresolved, 3) several life history and host characters are significantly associated with both the Eccrinida and Amoebidiidae phylogenies, providing platforms for future hypothesis formulation, 4) the protist trichos and the Eccrinida as a whole are likely much more species rich and widespread than what is currently known, 5) species delimitation within Paramoebidium is complicated by cryptic speciation, but there is evidence for possible host specificity, and 6) future studies of the protist trichos will benefit from an integrated approach that shifts away from an emphasis on the morphological species concept but includes both genetic sequence data and traditional morphological approaches

Manufacturing of poly(ethylene glycol diacrylate)-based hollow microvessels using microfluidics

The microvasculature is a vital organ that distributes nutrients within tissues, and collects waste products from them, and which defines the environmental conditions in both normal and disease situations. Here, a microfluidic chip was developed for the fabrication of poly(ethylene glycol diacrylate) (PEGDA)-based hollow self-standing microvessels having inner dimensions ranging from 15 μm to 73 μm and displaying biocompatibility/cytocompatibility. Macromer solutions were hydrodynamically focused into a single microchannel to form a concentric flow regime, and were subsequently solidified through photopolymerization. This approach uniquely allowed the fabrication of hollow microvessels having a defined structure and integrity suitable for cell culturing

REWILDING CHILDREN: Creating Digital Tools for K-5 Wildlife Education

As people are moving and expanding into more rural and unoccupied areas, the number of human-wildlife interactions have increased. Public attitudes toward wildlife are essential for the safety of both, as well as maintaining a healthy ecosystem. Lack of awareness and education surrounding wildlife results in relationships with wildlife becoming disconnected, dangerous, and harmful to both native wildlife species and people. We believe through proper education, these conflicts can be mitigated and prevented. With our literature review, we learned that starting education about wildlife at an early age is important. While some resources for teachers exist, they do not allow for students to interact with the material, nor feel empowered by it. Through the interviews that we conducted, we gained a greater understanding as to which subjects should be included in our curriculum on our website, where the current gaps are in education with wildlife and related topics, and what resources would be helpful to allow students to understand this material better. We interviewed a variety of people of different backgrounds, including parents, teachers, wildlife educators, scientists, and international scholars, in order to understand what to include in our created website. With this, we hope to educate children about the natural world and how they can interact with it, as well as develop a love and respect for nature and wildlife. This knowledge will give kids a head start in the science world and help them develop skills such as teamwork, problem-solving, reasoning, critical thinking, and collaborative skills when they are at their most impressionable age. This will be helpful for wildlife, and it will be vital in furthering education and developing skills they will take into their adult life

Terbinafine and risperidone drug interaction contributing to clinical changes in a forensic psychiatric patient

Risperidone is a second generation “atypical” antipsychotic that exhibits its clinical effects through a combined effort of risperidone and its active metabolite, 9-hydroxyrisperidone (9-OHR), otherwise known as paliperidone. Risperidone is hepatically metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme into 9-OHR. Significant interference with the metabolism of risperidone may lead to clinical consequences for patients via alterations in the ratio of the parent compound and active metabolite. This patient case reports 1 example of how a drug interaction could contribute to delayed response to a medication increase after psychiatric decompensation. A forensic psychiatric patient was transitioned from oral risperidone to risperidone microspheres long-acting injectable and had worsening of symptoms, necessitating an increased dose of the injection. This increase in symptoms may have been prolonged by addition of a CYP2D6 inhibitor, terbinafine. The changes in clinical symptoms correlate with medication concentrations that were drawn before terbinafine was started, during terbinafine therapy, and after terbinafine was discontinued

Hot topics, urgent priorities, and ensuring success for racial/ethnic minority young investigators in academic pediatrics.

BackgroundThe number of racial/ethnic minority children will exceed the number of white children in the USA by 2018. Although 38% of Americans are minorities, only 12% of pediatricians, 5% of medical-school faculty, and 3% of medical-school professors are minorities. Furthermore, only 5% of all R01 applications for National Institutes of Health grants are from African-American, Latino, and American Indian investigators. Prompted by the persistent lack of diversity in the pediatric and biomedical research workforces, the Academic Pediatric Association Research in Academic Pediatrics Initiative on Diversity (RAPID) was initiated in 2012. RAPID targets applicants who are members of an underrepresented minority group (URM), disabled, or from a socially, culturally, economically, or educationally disadvantaged background. The program, which consists of both a research project and career and leadership development activities, includes an annual career-development and leadership conference which is open to any resident, fellow, or junior faculty member from an URM, disabled, or disadvantaged background who is interested in a career in academic general pediatrics.MethodsAs part of the annual RAPID conference, a Hot Topic Session is held in which the young investigators spend several hours developing a list of hot topics on the most useful faculty and career-development issues. These hot topics are then posed in the form of six "burning questions" to the RAPID National Advisory Committee (comprised of accomplished, nationally recognized senior investigators who are seasoned mentors), the RAPID Director and Co-Director, and the keynote speaker.Results/conclusionsThe six compelling questions posed by the 10 young investigators-along with the responses of the senior conference leadership-provide a unique resource and "survival guide" for ensuring the academic success and optimal career development of young investigators in academic pediatrics from diverse backgrounds. A rich conversation ensued on the topics addressed, consisting of negotiating for protected research time, career trajectories as academic institutions move away from an emphasis on tenure-track positions, how "non-academic" products fit into career development, racism and discrimination in academic medicine and how to address them, coping with isolation as a minority faculty member, and how best to mentor the next generation of academic physicians