Binational/Cross-Cultural Health Enhancement

poster abstractThe Binational/Cross-Cultural Health Enhancement Center (BiCCHEC) fosters multidisciplinary research collaborations that address the biological, cultural, historical, legal, behavioral and demographic issues that impact the health status of communities where Hispanics are born and where they live in Indiana. BiCCHEC, with a commitment not only to research but also to teaching and service, develops and utilizes approaches, programs, training, and applications that are culturally relevant, practical, just, reciprocal, and always in partnership with communities. As communities become more and more diverse, obstacles to health and wellbeing created by language and cultural differences emerge. Finding ways to improve the availability of health services and eliminate health disparities for an increasingly diverse and mobile community is a commitment of the center. Since its 2007, BiCCHEC members have submitted sixty three internal and external grants of which thirty one have been funded for over $900,000. They have published 31 peerreviewed articles or book chapters and presented their research findings in 81 symposiums, showcases, workshops or conferences as keynote speakers, panel discussants or speakers. BiCCHEC projects are multidisciplinary; approximately 80% of the projects involve two or more IUPUI schools. BiCCHEC projects are also collaborative; approximately 70% of the projects have one or more community partners. BiCCHEC’s main community partners are La Plaza, Inc., the Institute for Mexicans Abroad (IME), Friends of Hidalgo, and more recently the Indiana Latino Institute. BiCCHEC conducts research with a commitment to service and education. Members have mentored 111 students in research and service-learning projects

Enhancement of Optical Coherence Tomography Images of the Retina by Normalization and Fusion

This paper describes an image processing method applied to Optical Coherence Tomography (OCT) images of the retina. The aim is to achieve improved OCT images from the fusion of sequential OCT scans obtained at identical retinal locations. The method is based on the normalization of the acquired images and their fusion. As a result, a noise reduction and an image enhancement are reached. Thanks to the resulting improvement in retinal imaging, clinical specialists are able to evaluate more efficiently eyes pathologies and anomalies. This paper presents the proposed method and gives some evaluation results

Definitive screening accelerates Taxol biosynthetic pathway optimization and scale up in Saccharomyces cerevisiae cell factories

Background: Recent technological advancements in synthetic and systems biology have enabled the construction of microbial cell factories expressing diverse heterologous pathways in unprecedentedly short time scales. However, the translation of such laboratory scale breakthroughs to industrial bioprocesses remains a major bottleneck. / Methods and Major Results: In this study, an accelerated bioprocess development approach was employed to optimize the biosynthetic pathway of the blockbuster chemotherapy drug, Taxol. Statistical design of experiments approaches were coupled with an industrially relevant high-throughput microbioreactor system to optimize production of key Taxol intermediates, Taxadien-5α-ol and Taxadien-5α-yl-acetate, in engineered yeast cell factories. The optimal factor combination was determined via data driven statistical modelling and validated in 1 L bioreactors leading to a 2.1-fold improvement in taxane production compared to a typical defined media. Elucidation and mitigation of nutrient limitation enhanced product titers a further two-fold and titers of the critical Taxol precursors, Taxadien-5α-ol and Taxadien-5α-yl-acetate were improved to 34 and 11 mg L-1, representing a three-fold improvement compared to the highest literature titers in S. cerevisiae. Comparable titers were obtained when the process was scaled up a further five-fold using 5 L bioreactors. / Conclusions: The results of this study highlight the benefits of a holistic design of experiments guided approach to expedite early stage bioprocess development

The pathway to secondary prevention of Alzheimer\u27s disease

Alzheimer\u27s disease (AD) is a continuum consisting of a preclinical stage that occurs decades before symptoms appear. As researchers make advances in investigating the continuum, the importance of developing drugs for secondary prevention is garnering increased discussion. For efficacious drug development for secondary prevention it is important to define what are the earliest biological stages of AD. The Alzheimer\u27s Association Research Roundtable convened November 27 to 28, 2018 to focus on pre-clinical AD. This review will address the biological approach to defining pre-clinical AD, detection, identification of at-risk individuals, and lessons learned from trials such as A4 and TOMMORROW

Systemic Sclerosis–Associated Interstitial Lung Disease: How to Incorporate Two Food and Drug Administration–Approved Therapies in Clinical Practice

Systemic sclerosis (SSc; scleroderma) has the highest individual mortality of all rheumatic diseases and interstitial lung disease (ILD) is among the leading causes of SSc-related death. Two drugs are now approved by the Food & Drug Administration (FDA) and indicated for slowing the rate of decline in pulmonary function in patients with SSc-ILD: nintedanib (a tyrosine kinase inhibitor) and tocilizumab (the first biologic agent targeting the interleukin-6 pathway in SSc). In addition, two generic drugs with cytotoxic and immunoregulatory activity, mycophenolate mofetil and cyclophosphamide, have shown comparable efficacy in a Phase II trial but are not FDA-approved for SSc-ILD. In light of the heterogeneity of the disease, the optimal therapeutic strategy in the management of patients with SSc-ILD is still to be determined. The objectives of this review are two-fold: (1) review the body of research focused on the diagnosis and treatment of SSc-ILD; and (2) propose a practical approach for diagnosis, stratification, management, and therapeutic decision-making in this clinical context. This review presents a practical classification of SSc patients in terms of disease severity (subclinical vs. clinical ILD) and associated risk of progression (low vs. high risk). The pharmacological and non-pharmacological options as first and second-line therapy, as well as potential combination approaches, are discussed in light of the recent approval of tocilizumab for SSc-ILD

Bayesian Inference For The Segmented Weibull Distribution

In this paper, we introduce a Bayesian approach for segmented Weibull distributions which could be a good alternative to analyze medical survival data in the presence of censored observations and covariates. With the obtained Bayesian estimated change-points we could get an excellent fit of the proposed model to any data sets. With the proposed methodology, it is also possible to identify survival times intervals where a covariate could have significantly different effects when compared to other lifetime intervals, an important point under a clinical view. The obtained Bayesian estimates are obtained using standard Markov Chain Monte Carlo methods. Some examples with real data sets illustrate the proposed methodology and its potential clinical value

Cardiogenic shock following administration of propofol and fentanyl in a healthy woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cardiogenic shock is very uncommon in healthy people. The differential diagnosis for patients with acute heart failure in previously healthy hearts includes acute myocardial infarction and myocarditis. However, many drugs can also depress myocardial function. Propofol and fentanyl are frequently used during different medical procedures. The cardiovascular depressive effect of both drugs has been well established, but the development of cardiogenic shock is very rare when these agents are used.</p> <p>Case presentation</p> <p>After a minor surgical intervention, a 32-year-old Caucasian woman with no significant medical history went into sudden hemodynamic deterioration due to acute heart failure. An urgent echocardiogram showed severe biventricular dysfunction and an estimated left ventricular ejection fraction of 20%. Extracorporeal life support and mechanical ventilation were required. Five days later her ventricular function had fully recovered, which allowed the progressive withdrawal of medical treatment. Prior to her hospital discharge, cardiac MRI showed neither edema nor pathological deposits on the delayed contrast enhancement sequences. At her six-month follow-up examination, the patient was asymptomatic and did not require treatment.</p> <p>Conclusion</p> <p>Although there are many causes of cardiogenic shock, the presence of abrupt hemodynamic deterioration and the absence of a clear cause could be related to the use of propofol and fentanyl.</p

Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma

Aberrant genetic and epigenetic variations drive malignant transformation and are hallmarks of cancer. Using PCR-free sample preparation we achieved the first in-depth whole genome (hydroxyl)-methylcytosine, single-base-resolution maps from a glioblastoma tumour/margin sample of a patient. Our data provide new insights into how genetic and epigenetic variations are interrelated. In the tumour, global hypermethylation with a depletion of 5-hydroxymethylcytosine was observed. The majority of single nucleotide variations were identified as cytosine-to-thymine deamination products within CpG context, where cytosine was preferentially methylated in the margin. Notably, we observe that cells neighbouring tumour cells display epigenetic alterations characteristic of the tumour itself although genetically they appear “normal”. This shows the potential transfer of epigenetic information between cells that contributes to the intratumour heterogeneity of glioblastoma. Together, our reference (epi)-genome provides a human model system for future studies that aim to explore the link between genetic and epigenetic variations in cancer progression.Cancer Research UK 236 (Grant ID: C14303/A17197), Wellcome Trust (Grant ID: 099232/z/12/z