Challenges in diagnosis of isolated central nervous system vasculitis

Isolated central nervous system (CNS) vasculitis is a rare and complicated disorder. Patients typically present with nonspecific neurologic symptoms such as headache and encephalopathy, and have variable progression and severity of the disease. Challenges to definitive diagnosis include the limitations of currently available diagnostic modalities with high likelihood of false-positive or false-negative findings. Imaging, serologic, and cerebrospinal fluid (CSF) evaluation, and even angiography can fail to establish the diagnosis. Often, brain biopsy is required. In order to illustrate these challenges, we report the case of a patient who presented with subacute cognitive decline and was ultimately diagnosed with isolated CNS eosinophilic vasculitis. Initial work-up included CSF and serologic analyses, magnetic resonance imaging (MRI), and cerebral angiography, but definitive diagnosis required brain biopsy. Immunosuppressive therapy resulted in clinical improvement and stabilization. To our knowledge, only one other case of isolated CNS eosinophilic vasculitis has been reported in the literature. We discuss the importance of a high index of clinical suspicion in cases of progressive nonspecific neurologic symptoms

Intravascular Lymphoma with Progressive CNS Hemorrhage and Multiple Dissections.

Introduction: Intravascular lymphoma (IVL) is an uncommon and often fatal disease characterized by intraluminal proliferation of lymphomatous cells within blood vessels. Because of a heterogeneous clinical presentation and lack of sensitive diagnostic protocols, diagnosis of IVL is most often made at autopsy. However, with early diagnosis and appropriate chemotherapy, the prognosis is greatly improved and complete remission is possible. In order to broaden the possible presentations of IVL, we present a patient with an atypical manifestation of biopsy-proven intravascular large B-cell lymphoma who suffered dissections of both intracranial and extracranial arteries in addition to progressive intracranial hemorrhages. Conclusion: IVL is known to exert its pathology on small arteries and capillaries, but is not known to cause dissections of large vessels. The diagnosis should be considered in cases with unexplained arterial dissections and progressive strokes. Early diagnosis with appropriate laboratory screening and tissue confirmation by biopsy can lead to greatly improved outcomes

Enriching Education with Exemplars in Practice: Iterative Development of Data Curation Internships

Partnerships between educational programs and research centers are vital to meeting the escalating workforce demands in data curation. They offer a platform for educators to increase their knowledge of current best practices and emerging challenges in the field. Student internships can be key to the success of these partnerships, not just for the students who gain authentic experience in facilities that excel at data intensive research and data services. Such partnerships provide an effective platform for rich and mutually beneficial engagement among educators, data professionals, scientists, and students. This paper reports on results from the Data Curation Education in Research Centers (DCERC) program aimed at developing a model for data curation education featuring field experiences in exemplar research centers. A strength of the DCERC model is its emphasis on facilitating mutual exchange of information among the DCERC program mentors and students. This model has evolved as a result of iterative and gradual refinements to the program model based upon information gathered from the formative evaluation. These refinements not only resulted in improved outcomes for the program participants but also, we believe, a more sustainable model for the program that leverages the knowledge base of the research scientists and students through peer-to-peer learning, rather than a traditional expert to trainee model. This paper describes formative evaluation findings that shaped the development of the DCERC program. We conclude with a discussion of the critical features of this model for the development of similar programs, and a data curation workforce that is able to accommodate and adapt to emergent data needs in a variety of environments

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease.

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease

Developing national CAREX projects in Latin America & the Caribbean : technical guide (annex) to the workshop proceedings “Building Capacity for CAREX Projects in Latin America and the Caribbean (Bogota, Colombia, May 2014)”

Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality in the Americas. These illnesses are responsible for substantial health and economic burdens; in the year 2012, non-communicable diseases accounted for approximately 73% of disability-adjusted life-years from all causes (1). Between 2006 and 2015 in Brazil alone, the cost of treatment and lost productivity due to five chronic diseases was an estimated $72 billion (2). Of the chronic health conditions that are prevalent in the Americas, cancer is among the leading causes of morbidity and mortality. Workplace exposures to known carcinogens are a cause of cancer, among other known and potential risk factors..

Serum carbon isotope values change in adults in response to changes in sugar-sweetened beverage intake.

Serum carbon isotope values [13C-to-12C serum carbon isotope ratio (δ(13)C)], which reflect consumption of corn- and cane-based foods, differ between persons consuming high and low amounts of sugar-sweetened beverages (SSBs). In this study, we determined whether serum δ(13)C changes in response to change in SSB intake during an 18-mo behavioral intervention trial. Data were from a subset of 144 participants from the PREMIER trial, a completed behavioral intervention (Maryland, 1998-2004). SSB intake was assessed using 2 24-h dietary recall interviews. Blinded serum samples were assayed for δ(13)C by natural abundance stable isotope mass spectroscopy. Multiple linear regression models with generalized estimating equations and robust variance estimation were used. At baseline, mean SSB intake was 13.8 ± 14.2 fl oz/d, and mean δ(13)C serum value was -19.3 ± 0.6 units per mil (designated ‰). A reduction of 12 oz (355 mL)/d SSB (equivalent to 1 can of soda per day) was associated with 0.17‰ (95% CI: 0.08‰, 0.25‰ P < 0.0001) reduction in serum δ(13)C values over 18 mo (equivalent to a 1% reduction in δ(13)C from baseline). After adjusting for potential confounders, a reduction of 12 oz/d SSB (equivalent to 1 can of soda per day), over an 18-mo period, was associated with 0.12‰ (95% CI: 0.01‰, 0.22‰ P = 0.025) reduction in serum δ(13)C. These findings suggest that serum δ(13)C can be used as a measure of dietary changes in SSB intake

Priority Setting for Occupational Cancer Prevention

Background: Selecting priority occupational carcinogens is important for cancer prevention efforts; however, standardized selection methods are not available. The objective of this paper was to describe the methods used by CAREX Canada in 2015 to establish priorities for preventing occupational cancer, with a focus on exposure estimation and descriptive profiles. Methods: Four criteria were used in an expert assessment process to guide carcinogen prioritization: (1) the likelihood of presence and/or use in Canadian workplaces; (2) toxicity of the substance (strength of evidence for carcinogenicity and other health effects); (3) feasibility of producing a carcinogen profile and/or an occupational estimate; and (4) special interest from the public/scientific community. Carcinogens were ranked as high, medium or low priority based on specific conditions regarding these criteria, and stakeholder input was incorporated. Priorities were set separately for the creation of new carcinogen profiles and for new occupational exposure estimates. Results: Overall, 246 agents were reviewed for inclusion in the occupational priorities list. For carcinogen profile generation, 103 were prioritized (11 high, 33 medium, and 59 low priority), and 36 carcinogens were deemed priorities for occupational exposure estimation (13 high, 17 medium, and 6 low priority). Conclusion: Prioritizing and ranking occupational carcinogens is required for a variety o

Oligodendroglial neoplasms with ganglioglioma-like maturation: a diagnostic pitfall

Although oligodendroglial neoplasms are traditionally considered purely glial, increasing evidence suggests that they are capable of neuronal or neurocytic differentiation. Nevertheless, ganglioglioma-like foci (GGLF) have not been previously described. Herein, we report seven examples where the primary differential diagnosis was a ganglioglioma with an oligodendroglial component. These five male and two female patients ranged in age from 29 to 63 (median 44) years at initial presentation and neuroimaging features were those of diffuse gliomas in general. At presentation, the glial component was oligodendroglioma in six and oligoastrocytoma in one; one was low-grade and six were anaplastic. A sharp demarcation from adjacent GGLF was common, although some intermingling was always present. The GGLF included enlarged dysmorphic and occasionally binucleate ganglion cells, Nissl substance, expression of neuronal antigens, GFAP-positive astrocytic elements, and low Ki-67 labeling indices. In contrast to classic ganglioglioma, however, cases lacked eosinophilic granular bodies and CD34-positive tumor cells. Scattered bizarre astrocytes were also common and one case had focal neurocytic differentiation. By FISH analysis, five cases showed 1p/19q codeletion. In the four cases with deletions and ample dysmorphic ganglion cells for analysis, the deletions were found in both components. At last follow-up, two patients suffered recurrences, one developed radiation necrosis mimicking recurrence, and one died of disease 7.5 years after initial surgery. We conclude that GGLF represents yet another form of neuronal differentiation in oligodendroglial neoplasms. Recognition of this pattern will prevent a misdiagnosis of ganglioglioma with its potential for under-treatment